Tofersen 臨床和患者報告結局及神經絲反應

肌肉神經。2024年9月；70(3):333-345。

doi: 10.1002/mus.28182。電子版發布日期：2024年6月20日。

SOD1相關ALS患者接受托弗森治療期間的臨床和患者報告結局及神經絲反應——一項為期18個月的多中心觀察性研究

摘要

引言/目的：在SOD1突變引起的肌萎縮側索硬化症(ALS) (SOD1-ALS)中，托弗森在美國獲得了加速批準，並可通過美國以外的擴展獲取計劃(EAP)獲得。這項多中心研究旨在探討德國一項擴展獲取計劃(EAP)中托弗森治療期間的臨床和患者報告結局(PRO)以及血清神經絲輕鏈(sNfL)。

方法：分析了16例接受托弗森治療至少6個月的SOD1-ALS患者。研究了ALS進展率（ALS-PR），以ALS功能評定量表修訂版（ALSFRS-R）、慢肺活量（SVC）和sNfL的月變化量來衡量。PRO包括自我測量醫療結果量表（MYMOP2）、藥物治療滿意度問卷（TSQM-9）和淨推薦值（NPS）。

結果：托弗森平均治療時間為11個月（6-18個月）。ALS-PR平均變化量為-0.2（範圍0至-1.1），相對降低25%。7例患者ALSFRS-R升高。SVC保持穩定（平均88%，範圍-15%至+28%）。除1例雜合D91A-SOD1突變攜帶者外，所有患者的sNfL均降低（sNfL平均變化量為-58%，範圍-91%至+27%，p < .01）。 MYMOP2 表明症狀嚴重程度有所改善（n = 10）或仍有部分緩解（n = 6）。TSQM-9 顯示總體治療滿意度較高（平均值 83，標準差 16），盡管給藥便利性一般（平均值 50，標準差 27）。NPS 顯示托弗森的推薦率非常高（NPS +80）。

討論：本 EAP 數據支持 SOD1-ALS 患者對托弗森的臨床和 sNfL 反應。PRO 表明患者對托弗森治療在臨床實踐中的良好感受。

Muscle Nerve . 2024 Sep;70(3):333-345.

 doi: 10.1002/mus.28182. Epub 2024 Jun 20.

Clinical and patient-reported outcomes and neurofilament response during tofersen treatment in SOD1-related ALS-A multicenter observational study over 18 months

 

bstract

Introduction/aims: In amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (SOD1-ALS), tofersen received accelerated approval in the United States and is available via expanded access programs (EAP) outside the United States. This multicenter study investigates clinical and patient-reported outcomes (PRO) and serum neurofilament light chain (sNfL) during tofersen treatment in an EAP in Germany.

Methods: Sixteen SOD1-ALS patients receiving tofersen for at least 6 months were analyzed. The ALS progression rate (ALS-PR), as measured by the monthly change of the ALS functional rating scale-revised (ALSFRS-R), slow vital capacity (SVC), and sNfL were investigated. PRO included the Measure Yourself Medical Outcome Profile (MYMOP2), Treatment Satisfaction Questionnaire for Medication (TSQM-9), and Net Promoter Score (NPS).

Results: Mean tofersen treatment was 11 months (6-18 months). ALS-PR showed a mean change of -0.2 (range 0 to -1.1) and relative reduction by 25%. Seven patients demonstrated increased ALSFRS-R. SVC was stable (mean 88%, range -15% to +28%). sNfL decreased in all patients except one heterozygous D91A-SOD1 mutation carrier (mean change of sNfL -58%, range -91 to +27%, p < .01). MYMOP2 indicated improved symptom severity (n = 10) or yet perception of partial response (n = 6). TSQM-9 showed high global treatment satisfaction (mean 83, SD 16) although the convenience of drug administration was modest (mean 50, SD 27). NPS revealed a very high recommendation rate for tofersen (NPS +80).

Discussion: Data from this EAP supported the clinical and sNfL response to tofersen in SOD1-ALS. PRO suggested a favorable patient perception of tofersen treatment in clinical practice.